History Of Keratoconus Research

There have been milestone discoveries that have furthered the research efforts in KC. We know that keratoconus is a noninflammatory, thinning condition of the cornea. In 1963, scientists found that the initial changes of KC were related to degradation (break down) of the cornea¹s basement membrane.  See Fig. 1 for a diagram of the layers of the cornea. They found that over time, a cascade of events occurred, leading to alterations in the layers of the cornea and resulting in the thinning of the stromal layer. This weakened the structural integrity of the cornea and in turn resulted in a bulging, cone-like distortion of the normally spherical cornea.

Figure 1

Fig. 1: LAYERS OF THE CORNEA
Prior to 1985, investigators reported very confusing and often contradictory results about KC corneas. Then Dr. Yue and coworkers at the laboratory at the Univ. of IL/Chicago, showed that KC corneas were heterogeneous (were not uniformly alike, and had individual differences). Therefore, it was necessary to analyze single KC corneas instead of pooling the corneas together in laboratory experiments.

The combining of tissues probably accounted for the contradictory results in the literature. Since that time, scientists have analyzed corneas individually and reported accordingly.

Attention then turned to the thinning aspects of KC corneas. Investigators found that the enzyme activities of the KC corneas were increased compared to normal corneas. In addition, there was a significant reduction of inhibitors for these enzymes.  In a completely different area of study, scientists in the Netherlands examined the processing of free radicals and their enzymes in the KC corneas.

The cornea is responsible for approximately 80% of the absorption of ultraviolet B (UVB) light that enters the eye. UV light generates free oxygen radicals, high energy molecules, which if unchecked, can damage tissue. Typically, the free radicals are removed from the cornea via antioxidants (such as superoxide dismutase, catalase and glutathione reductase).

These enzymes are resident in normal corneal tissue and ward off the detrimental effects of the free radicals. However, they do not always remove all of the free radicals. Those that are not removed undergo reactions that form aldehydes, which can be destructive to the tissue.

Normally, the cornea protects itself from these aldehydes with an enzyme called aldehyde dehydrogenase (ALDH) which detoxifies these aldehydes. ALDH is a major protein within the cornea. (Approximately 78% of the ALDH within the eye is found in the cornea.). In the KC cornea there is decreased activity of ALDH enzyme. Therefore, if the ALDH is decreased in KC, then it is reasonable to conclude that there may be an increased level of destructive aldehydes in KC corneas.

Figure 2

 

(Fig. 2)

 

Reviewed 2012

Dr. Kenney is Professor and Director of Ophthalmology Research, Ophthalmology School of Medicine at the University of California-Irvine in Irvine, CA.

Learn about the milestones in keratoconus research since 1963.